He wanted to shut down the stress response, since he saw that patients were killed by the endogenous mechanisms supposed to protect them from shock. This worked well, but made him a medical heretic to his colleagues! The Laborit cocktail or cocktail lytique was the combination of promethazine, pethidine, and chlorpromazine, and this was later called neuroleptanalgesia. Inhibitors,research,lifescience,medical During surgical procedures, the patients were calm, still capable of obeying simple orders, and had fewer selleck variations of blood pressure, although this effect

of surgery did persist. Laborit developed further the technique of hypothermia, associated with chlorpromazine, and concluded that this provided protection against the toxicity of stress responses during anesthesia and surgery. The indifference observed under chlorpromazine led to trials in agitated patients, by a small group of psychiatrists, advised by Laborit. Jean Delay and Pierre Deniker described the effects of the molecule in manic psychosis and mental confusion.4 Laborit also worked on the toxicity of oxygen. He was Inhibitors,research,lifescience,medical asked to do this by the army because of the toxicity of oxygen in divers. The synthesis of gamma-OH emerged this work, with the intention of finding a γ-aminobutyric acid (GABA)-like compound that would cross the blood-brain barrier. The idea was that since glial cells Inhibitors,research,lifescience,medical had few mitochondria, and neurons

had many, the former helped the latter, and neurons could be indirectly helped by facilitating the pentose pathway in glial cells. This was a precursor in the field of free radical research and therapy. Gamma-OH was used in delirium tremens, in anesthesia after head trauma, in insomnia, and is still prescribed in Inhibitors,research,lifescience,medical narcolepsy. The antidepressant Agr 1240 (minaprine, marketed as Cantor® until 1990) was a stimulating molecule that Laborit developed with the idea of neutralizing the consequences of inhibition of action. Inhibition of action A major role of the brain is to organize behaviors, ie, action. There is inhibition Inhibitors,research,lifescience,medical of action when behaviors become impossible, and this is deleterious to health. This happens

when an instinctive behavior (such as fight or flight) is impossible, when acting is useless, when a and danger cannot be predicted, or when no previous response pattern exists to direct action. In these situations, a brain system, the système inhibiteur de l’action, or behavioral inhibition system (BIS), is activated and stimulates the neuroendocrine responses that were described by Walter Cannon in the 1920s and Hans Selye in the 1930s and 1940s. Inhibition of action is illustrated in animal experiments that we carried out in Laborit’s laboratory during the early 1970s. Rats were placed in an activity-avoidance conditioning apparatus with two compartments. Rats received 10 cycles of 21 plantar electric shocks daily for 1 week, each shock session being preceded by a light and sound warning stimulus.